This invention relates to antibodies and antigen-binding portions thereof that bind to human IL-6. This invention also relates to nucleic acids encoding such antibodies and antigen binding portions thereof; methods of making such antibodies and antigen binding portions thereof; compositions comprising such antibodies or antigen binding portions thereof; and uses of such antibodies or antigen binding portions thereof.
Interleukin-6 (IL-6), which is also known as interferon B2 (IFNB2), is a pleiotropic cytokine that belongs to the family of gp130 ligands and is produced by many cell types, including T lymphocytes, fibroblasts and monocytes. IL-6 is produced constitutively at low levels and is readily induced by infectious stimuli or inflammatory cytokines. IL-6 binds to a specific receptor IL-6R (gp80) which heterodimerizes with cell-bound or soluble gp130 to form a functional receptor complex. Binding of IL-6 to its receptor initiates cellular events including activation of the JAK-STAT3 pathway and ras-mediated MAP kinase signaling. IL-6 can elicit a diverse array of effects such as proliferation and differentiation of B cells and monocytes, T cell activation, hematopoiesis, osteoclast activation, keratinocyte growth, neuronal growth, hepatocyte activation and acute phase protein induction from hepatocytes.
IL-6 plays an important role in B cell abnormalities as demonstrated in systemic lupus, erythematosus, multiple myeloma and lymphoproliferative disorders. Similarly, IL-6 is also implicated in the pathogenesis of autoimmune and inflammatory diseases such as rheumatoid arthritis and osteoarthritis. Recently, indirect evidence suggests an association between IL-6 and chronic obstructive pulmonary disease and insulin resistance in type 2 diabetes. IL-6 has both pro-inflammatory and anti-inflammatory effects in the immune system, indicating that this cytokine likely plays a central role in regulating the physiological response to disease. Therefore, targeting IL-6 can potentially provide therapeutic benefit in a variety of disease areas.
An increase in the production of IL-6 has been observed in a number of diseases including: Alzheimer's disease, autoimmune diseases, such as rheumatoid arthritis, inflammation, myocardial infarction, Paget's disease, osteoporosis, liver fibrosis, solid tumors (renal cell carcinoma), prostatic and bladder cancers, neurological cancers, and B-cell malignancies (e.g., Casteleman's disease, certain lymphomas, chronic lymphocytic leukemia, and multiple myeloma). Research has indicated that IL-6 is linked to the pathogenesis of many of these diseases, particularly, cancer and rheumatoid arthritis and, therefore, blocking IL-6 should translate into clinical benefits.